Nearly 77% of the US population is now overweight. This dramatic change in the last 50 years is correlated with the availability of highly processed foods, and with a dramatic increase in chronic pain.
In a mouse model, high-calorie foods, which induces a dopamine release, disrupted normal feeding schedules, resulting in overconsumption.
Additionally, the “knockout” mouse model which had dopamine signaling disrupted, didn’t seek the dietary “rewarding pleasure,” maintained a normal eating schedule, and did not become obese.
Practical Conclusion:
Diet-induced obesity requires dopamine (DA)-Drd1 signaling
Avoid eating outside a normal eating window, typically less than eight hours out of 24, allowing glycogen depletion in the liver and preventing insulin resistance.
How is this relevant to chronic pain:
I practice in the field of interventional pain, addiction, and obesity/ metainflammation.
1. Patients with chronic pain have a signaling mechanism, whether induced by medications or their endogenous pain, that causes them to seek out dopaminergic stimulation, to relieve their pain.
2. Some of these dopaminergic stimulation can be substituted by dietary intake.
3. Excessive non-nutritive dietary intake leads to obesity and visceral adipose tissue accumulation, which is inflammatory.
4. Excessive inflammatory mediators aggravate pain, and the cycle repeats.
I operate an interventional pain clinic in the urban core. More than 90% of my chronic pain patients have metabolic dysfunction and have always presumed that the Standard American Diet was to blame for their metabolic syndrome and subsequent metainflammation. Even the ones who do not have high waist circumference still had elevated fasting glucose and elevated HgBA1C.
I have noticed a pattern that seems unusual, and counterintuitive.
I assumed that a “clean” vegan diet would have “fewer toxins” and therefore patients would more quickly heal from chronic pain pathologies. The primary reason patients give me this dietary choice was a desire to improve health, lose weight, and avoid diabetes.
I have noticed that my male patient’s who are long-term vegan, for more than three years, seems to have more sarcopenia (muscle wasting) and have clinical and laboratory hypogonadism. Their LDL-C is typically low, as one would expect, but their Omega 6:3 ratios are very high (typically >20). The male long-term vegan patient seems to be clinically thin and yet metabolically obese, with multiple deficiencies in fat-soluble vitamins, specifically D and K.
I also find that this specific population has a harder time retaining muscle mass during strengthening, and almost all of them require testosterone supplementation. I don’t notice this in patients who are vegans for less than one year.
I recognize that “veganism is more than a diet; it is a philosophy and ethic.” Attempting to adequately supplement Omega 3, Vitamin D and K, and cholesterol for gonadal hormone formation is challenging in the strict vegan population.
I welcome any suggestions.
Dr. Gurpreet Padda
My clinic started as an interventional pain clinic, but I quickly realized that chronic pain was more than an isolated pathology of excessive pain. I have amazing tools that can relieve a patient’s symptoms, but I can’t reverse the course of the disease unless I treat the underlying cause, the metainflammation. Pain simply doesn’t become chronic in metabolically healthy people.
Unfortunately, less than 12.2% of the US population is metabolically healthy and more than 60% are overweight or obese.
Chronic diseases driven by obesity accounts for >$480 B direct costs. The total cost of chronic diseases due to obesity is > $1.7 T (about 9.3% of the US GDP or 47% of the total cost of chronic disease spending nationwide). These are MASSIVE costs, and overtime WILL BANKRUPT the US economy.
I believe that failing to treat the patient’s underlying pathology, the cause of the patient’s symptoms, is a disservice to the patient and to society.
Patients rarely seek preventative treatment, they most often wait for their symptoms to manifest, and pain is the cardinal symptom that drives them to seek care. Pain after all is the body signaling mechanism of impending tissue damage. Patients are also highly motivated and receptive to lifestyle changes when confronted with a lifetime of painful suffering.
I still have an interventional pain clinic, but now the interventions include lifestyle and chronic disease interventions that provide patients with tools and techniques to reverse metainflammation. We have gone from treating the patient in isolation to treating the community around the patient, to maintain adherence to lifestyle changes.
Not all food is created equal, and some are even more (ultra) processed than others, thus contributing to gut dysfunction. The purpose of ultra-processing food is to create branded, convenient (durable, ready to consume), attractive (hyper-palatable), and profitable (low-cost ingredients) food products.
Ultra-processed food is made from food-like substances and additives, with little intact natural food. These ingredients are not normally used in natural culinary preparations.
Additives include preservatives, antioxidants, and stabilizers to reduce normal degradation and lengthen shelf life. Some additives enhance the sensory qualities of foods or disguise unpalatable aspects of the final product (dyes and other colors, color stabilizers, flavors, flavor enhancers, non-sugar sweeteners). Processing additives (such as carbonating, firming, bulking, and anti-bulking, de-foaming, anti-caking, and glazing agents, emulsifiers, sequestrants, and humectants) increase gut permeability. Processing with heat extrusion can create de novo compounds, some of which are carcinogens. The preparation and milling of food into shelf-stable acellular materials increases the rapidity of gut absorption, contributing to hepatic dysfunction.
Ultra-processed foods makeup 57.9% of dietary intake and contribute 89.7% of the energy intake from added sugars. These empty-calorie foods contain minimal bioavailable essential nutrients and displace more nutrient-dense foods, which leads to an overfed and yet undernourished population.
Consuming ultra-processed food leads to metainflammation through gut dysfunction. Metainflammation is the root cause of most diseases of Western civilization: obesity, diabetes, heart disease, cancer, cognitive decline, autoimmune dysfunction, and chronic pain.
Many people think that sugar is sugar, but there are different types and sugar comes in many forms. Compared with glucose, fructose plays a primary role in development of metainflammation, obesity, prediabetes, and type 2 diabetes
Fructose directly increases de novo lipogenesis, promotes dyslipidemia, decreases insulin sensitivity, increases visceral adiposity, and stimulates the reward center, similar to cocaine.
What is sugar?
Because glucose is the sugar that we most often talk about and measure in diabetics, most people assume that their regular table sugar is made of glucose. However, common table sugar is actually a disaccharide, made of two monosaccharides, fructose and glucose, bonded together in a 1:1 ratio.
High fructose corn syrup (HFCS) contains about 5% more fructose than glucose. HFCS is manufactured by hydrolyzing corn starch into glucose, which then is isomerized into fructose. Fructose is preferred by food and soft drink manufacturers because fructose exerts a significantly increased perception of sweetness and likely because its production is subsidized. Glucose has a sweetness index of 74 compared to sucrose of 100 or fructose of 173.
According to the CDC, over 30 million Americans have diabetes, with 1 in every 4 not knowing their diagnosis. Fructose is more strongly linked to obesity and diabetes than glucose. There is no biochemical reaction in any eukaryotic organism that requires fructose.
Metabolism of glucose and fructose
Glucose can be utilized as an energy source by almost every cell in the body. Only the liver can metabolize fructose, and it will preferentially convert fructose into fat storage. The body has the ability to handle a small amount of fructose at a time, without adverse health consequences. Fructose does come naturally from fruits, but the absorption is slow due to the large amount of fiber. Unfortunately, removing the fiber by juicing or destroying the fiber, as done in a smoothie, dramatically increases the speed of absorption, overwhelming the liver and sending a fructose rush to the brain.
Glucose consumption normally causes insulin release from the pancreas. Insulin acts on surface cell receptors, which allow glucose absorption into the cell for energy use or converting it to fat inside the cell. High levels of insulin, in the presence of high levels of glucose, cause a liver enzyme [phosphofructokinase PFK] to convert glucose to fructose, which is then quickly turned into fat storage and not used for energy production. However, if you directly ingest fructose, it bypasses the enzyme gateway and insulin is not released, and it goes straight to fat storage.
The metabolism of fructose differs from that of glucose, with liver metabolism of fructose favoring de novo lipogenesis [fat production directly from fructose]. Additionally, fructose does not stimulate insulin secretion or leptin production. Insulin normally regulates the absorption of sugar into the cells, and leptin normally notifies brain receptors that you are full. Because insulin and leptin act as key signals in the regulation of food intake and body weight, fructose consumption causes yet further hunger and additional weight gain. The body is rapidly storing fat, and doesn’t know it’s full.
Insulin resistance from fructose and the beginning of metabolic inflammation
Fructose can also directly trigger insulin resistance. When mice are fed with excessive amounts of fructose, they produce carbohydrate responsive element-binding protein, or ChREBP, which blocks the liver from responding to the insulin.
Fructose is 20 times more likely to cause fatty liver (the key problem of insulin resistance) compared to glucose alone. Fructose feeding studies, replacing glucose with a calorically equal amount of fructose, document a 5x increase in de novo lipogenesis and an increased liver fat by 38% within eight days.
[The metabolism of ethanol (alcohol) is similar to that of fructose. Nearly 80% of the ingested ethanol is delivered to the liver, and metabolized to acetaldehyde, which also stimulates de novo lipogenesis.]
Fructose overfeeding can provoke insulin resistance. Healthy subjects overfed 1000 calories per day of fructose demonstrated a 25 percent worsening of their insulin sensitivity in seven days.
Fructose induces insulin resistance even at typical consumption doses, in less than eight weeks. Subjects were fed 25 percent of their daily calories as Kool-Aid sweetened with either glucose or fructose. The fructose group increased their insulin resistance, and could be clinically classified as pre-diabetic. The glucose group did not.
Fructose engages in the Maillard reaction, or glycation seven times faster than glucose, and a metabolite of fructose does it 250 times faster. We commonly measure this as HgBA1C for glucose. The measure for fructose is fructosamine. This glycation effect makes the cell walls sticky, and the receptors not work. This may explain why patients with high glycation levels require more pain medication, because their receptors simply don’t work. It also is part of the explanation how insulin resistance occurs.
Fructose and addiction
Fructose stimulates the reward center of the brain while glucose does not. Data suggests that the fructose molecule in sugar is what it makes it addictive.
- Glucose activates the cortex, the basal ganglia, and certain other parts, but not the limbic system. Glucose results in a sensation of serotonin-induced happiness. By contrast, fructose stimulates the limbic system and is associated with increased dopamine release in the nucleus acumbens, similar to other addictive drugs (glucose does not stimulate the nucleus acumbens). Fructose results in a sensation of dopamine-induced pleasure.
Agricultural subsidies
Governmental subsidies were initially a method to subsidize farmers during the Depression and the Dust Bowl in 1933. We had a destitute population in the American southwest, dying of famine. Most of the the food and food manufacturers were in the Northeast. By the time it took to transport food by rail to the Southwest, it would go rancid. They had to process it: remove the fiber from the wheat, package it in 5 pound bags, ship it to the Southwest, and then bake it locally. The subsidy was designed to make it worthwhile for the American food industry to invest in a processing and distribution system for a famine-stricken population, which made sense through World War 2.
Unfortunately, President Nixon, concerned about re-election, knew that fluctuating food prices caused political unrest. Nixon instituted a policy of maintaining low consumer prices for food by agricultural subsidy. Until that point, our subsidies were actually designed to pay farmers to not grow certain crops and maintain inflated prices. This policy also allowed the soil to regain nutrient after crop harvest. His agriculture secretary, Rusty Butz, changed farming operations so soil was no longer left fallow; there was no time to restore nutrient after a crop was harvested. It also encouraged monocropping and megafarms. Subsidies have created an agricultural farmer dependency on governmental support. The massive overproduction of just a few grain items resulted in a huge surplus and difficulty in long-term storage. Distributing this slowly rotting surplus was solved through the food stamp system, creating a consumer dependency on governmental support. Unfortunately, these processed staple items are carbohydrate-rich, but have had most of their fiber stripped and fat removed to prevent rancidity, and lack much of the soil-derived micronutrients.
Governmental subsidies and import tariffs have resulted in corn being a much more economical sweetener than sugar–a trend that is not seen in other parts of the world. The consumption of HFCS increased by more than 1000% between 1970 and 1990, far exceeding the changes in intake of any other food or food group. HFCS now represents more than 40% of caloric sweeteners added to foods and beverages, a daily average of 132 calories per person. The effect of governmental subsidy is most evident when you compare the same soft drink in the United States to one in Mexico; for example, Coke contains corn syrup as the sweetener in the United States while it contains cane sugar in Mexico.
The per capita consumption of high fructose corn syrup — the primary sweetener in soft drinks and other sweetened beverages — has increased from 38.2 pounds in 1980 to 868 pounds in 1998 (Chou et al., 2004). In 1942, annual U.S. production of soft drinks was 90 8 oz. servings per person; in 2000, it was 600 servings (Jacobson, 2005).
Other names for sugars:
Processed foods will most likely have sugars added. Unfortunately, they can go by any number of names. While this is an extensive list, it is not complete. The more naturally you can eat your foods, the better success you will have with creating a permanent weight loss solution.
Agave Syrup
Amasake
Any name ending in “ose” or “ol” or “syrup”
Barbados Sugar
Barley Malt
Blackstrap Molasses
Black Sugar
Brown Sugar
Cane Juice or Cane Juice Crystals
Cane Sugar
Caramel or Caramel Coloring
Castor Sugar
Confectioner’s Sugar
Corn Sweetener
Corn Syrup – a manufactured syrup of corn
starch, containing varying proportions of glucose
maltose, and dextrose
Corn Syrup Solids
Crystallized Cane Juice
D-mannose
Date Sugar
Demerara
Demerara Sugar
Dehydrated Cane Juice or Dehydrated Cane
Juice Crystals
Dextran
Dextrin
Dextrine
Dextrose (glucose) – a simple sugar made of
only one molecule
Erythritol
Evaporated Cane Juice
Evaporated Cane Juice Sugar
Florida crystals (a trademarked name)
White or Brown Sugars
Fructose – a simple sugar refined from fruit
Fruit Juice Concentrate
Galactose or Galatactose
Glucose or Glucose Syrup
Golden Syrup
Grape Sugar
Grape Juice or Grape Sweetener
High Fructose Corn Syrup (HFCS)
Honey
Hydrolysed or Hydrolyzed Starch
Hydrogenated Glucose Syrup
Hydrogenated Starch Hydrolysates (HSH)
Invert Sugar
Isomalt
Levulose
Lactitol or Lactital
Lactose – a simple sugar from milk
Malt
Malt Extract
Malt Syrup
Maltodextrin
Maltose
Malitol
Maple Syrup
Molasses
Monosaccharide
Muscovado
Organic Dehydrated Cane Juice
Organic Brown Sugar
Panocha
Polysaccharide
Powdered Sugar
Raw Cane Crystals
Raw Honey
Raw Sugar